What does it mean to put new hepatitis C drugs on a list of essential medicines?BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i2035 (Published 22 April 2016) Cite this as: BMJ 2016;353:i2035
- Julian Urrutia, MD and PhD candidate1,
- Thalia Porteny, PhD candidate1,
- Norman Daniels, professor in health policy2
- 1Interfaculty Initiative in Health Policy, Harvard University, Cambridge, MA 02138, USA
- 2Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, MA, USA
- Correspondence to: J Urrutia
New direct acting antiviral drugs to treat hepatitis C infection are highly effective. Sofosbuvir and velpatasvir have been shown to achieve 90-100% cure rates regardless of hepatitis C virus (HCV) genotype.1 They are also very expensive, commanding list prices that can exceed $1000 (£700; €880) a day. Nevertheless, studies have shown that treating everyone infected with HCV in the United States is cost effective from a societal perspective.2 Moreover, manufacturers are already offering substantial discounts. Advocates are thus demanding that these drugs should be made available for everyone infected with HCV.1 3 4 The World Health Organization (WHO) recently added sofosbuvir, along with other highly expensive medicines, to its model list of essential medicines.5 6 However, HCV infection is so common that covering these drugs for all who might benefit is not a realistic option for most health systems, even if the price were $1 per pill, which is the estimated minimum cost of production,7 8 rather than $1000. So how should countries respond?
Essential medicines and priority setting
Inclusion on the list does not mean that every country should guarantee access to everyone who might benefit, regardless of cost. WHO defines essential medicines as “those that satisfy the priority healthcare needs of the population.” Yet the agency also notes that “essential medicines are intended to be available … at a price that the individual and the community can afford,” adding that the list is not designed to be a global standard but a “guide for the development of national and institutional essential medicine lists” (box 1).9 10 This intentional ambiguity leaves room for countries to interpret which health needs have “priority” and which medicines are “affordable.”11
Essential medicines are those that satisfy the priority healthcare needs of the population
Criteria for selection of essential medicines
Essential medicines are selected with due regard to disease prevalence, evidence on efficacy and safety, and comparative cost effectiveness
Essential medicines list
Essential medicines are intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford. WHO’s model list is a guide for the development of national and institutional essential medicine lists. It was not designed as a global standard. However, for the past 30 years the model list has led to a global acceptance of the concept of essential medicines as a powerful means to promote health equity. Most countries have national lists, and some have provincial or state lists as well. National lists of essential medicines usually relate closely to national guidelines for clinical practice, which are used for the training and supervision of health workers.
This is not the first time that WHO has added expensive medicines to its model list (table 1⇓). When 12 antiretroviral drugs for HIV/AIDS were added in 2002, few countries could afford them. Countries respond differently to a drug’s inclusion on WHO’s list. Only 20% of low and middle income countries have listed docetaxel (an expensive cancer drug added in 2011) on their national list, and 70% have listed amphotericin B (an inexpensive antifungal added in 2007).25 26 Inclusion on the WHO list can help mobilise international commitment (and resources) for important causes, as with antiretrovirals. But it can also put non-benign pressure on countries: when there is a legal right to healthcare, courts are prone to favour plaintiffs seeking drugs that are on the model list but not on the country’s list.27
Countries have different priorities and capacities for meeting population health needs. Therefore, they have to clarify the intended goals of covering new drugs and justify their opportunity costs. Covering new hepatitis drugs must fit with other decisions about health system priorities, and some restrictions on how these drugs are made available are consistent with reasonable prioritisation decisions. Rather than providing treatment to everyone, countries may decide that their goal is to reduce HCV related morbidity and mortality or to provide rescue therapy for patients with life threatening illness who have exhausted all other therapeutic possibilities. Some countries may decide that they cannot reasonably cover these treatments for anyone, even if only as rescue therapy, because doing so would require forgoing other treatment that would save more lives or produce more equality.
The increased safety and convenience of the new drugs could simplify management of hepatitis C, making it possible to provide broad access through primary care. As table 2⇓ shows, however, the cost of sofosbuvir for all patients infected with HCV is unaffordable for most countries, even with the hundredfold price discounts offered to some low income countries.2 Measures that increase the competitiveness of purchasing actions could further reduce prices, but this will not adequately counter the effect of high HCV prevalence on cost. Moreover, table 2⇓ necessarily underestimates the full opportunity cost of treating all infected patients, since it only reflects drug purchasing costs without taking into account any other expenses that countries would have to shoulder.28
Fortunately, countries can also substantially improve population health by focusing on patients at high risk of developing severe liver disease rather than treating everyone infected. This option is far less costly because many infected patients are years away from developing clinically relevant liver disease. It is also more cost effective: studies show that, in the US, using sofosbuvir to treat people without liver fibrosis can cost $173 796 per quality adjusted life year (QALY) gained compared with $35 884/QALY for patients with severe fibrosis.2
An even more affordable approach is to restrict use to patients who have exhausted all other therapeutic possibilities. Each of these increasingly narrower goals could be justified provided that everyone agrees that they are relevant to meeting health needs fairly.
Setting limits fairly
Some wealthy countries might attempt to provide broad access to direct acting antivirals. For example, in the UK the debate is not about whether to scale up access but about what is the most cost effective way of doing so.29 However, most health systems (including some in high income countries such as Spain and the United States) are restricting access on the basis of disease severity or need for rescue therapy.30 31
Some restrictions might be justified. Others would clearly be arbitrary or discriminatory. For example, if the goal is to reduce morbidity and mortality, limiting access for drug users—as most state Medicaid programmes in the US have done—may be counterproductive since these groups generally have a high burden of HCV related disease.29 31 Such restrictions do not seem to follow from reasons that are relevant from a medical or public health perspective but from concerns that certain people are less deserving of resources despite the consequences of that denial. More generally, placing restrictions on coverage through Medicaid while other health plans provide broader coverage creates a two-tiered system with problematic inequalities.
Cost effectiveness may be an important criterion for inclusion on the list, but it is not a sufficient condition for national selection by countries. To decide whether an allocation is reasonable one must take into account its full opportunity cost, which requires balancing concerns about cost effectiveness, priority to the worst off, and financial risk protection, among other considerations that may be relevant in a particular context.
Cost effectiveness analysis has an important role in the deliberations about which goals to pursue and how. For example, if older drugs are more cost effective than new direct acting antivirals a country that has decided the goals of reducing HCV related morbidity and mortality and providing rescue treatment are worth the opportunity cost might rely on the older drugs for treating patients who can benefit from them, covering the newer drugs only for patients who do not respond to or cannot tolerate the older ones. However, even this strategy is only reasonable if there is equal access to the older, cheaper treatments. Groups that are typically underserved by the health system and that tend to have a greater burden of HCV (such as drug users, prisoners, men who have sex with men, and some marginalised racial or ethnic groups) may reasonably demand that inequities in access to the older treatments should be fixed before the newer drugs are made available to the general population. Since effects on equity are part of the opportunity cost of expanding access to direct acting antivirals, they also need consideration.
The preceding arguments are especially relevant in countries that recognise a legal right to health (or healthcare), as many low and middle income countries do. It would be a mistake to assume that such a right implies that anyone who might benefit is entitled to any drug on WHO’s list. Judicial involvement may encroach on the task of deciding whether the goals that could be achieved with a listed drug are more important than other goals that could be achieved instead. Courts are not well positioned to assume such a task, as they lack the information and expertise needed to evaluate opportunity costs. Moreover, relying on courts may aggravate existing inequalities in health and access to care because there are also social inequalities in access to the courts. (Some may believe the courts are less subject to capture by vested interests than health systems themselves, but this belief is hard to support with evidence.)
We have argued elsewhere that the courts should show due deference to the health system, which is generally society’s designated agent for deciding how best to use limited resources to promote population health and distribute it fairly.32 Courts are more likely to show due deference if a country establishes a fair and transparent deliberative process for deciding on resource allocation. Such a process should make the rationales for allocative decisions public so that courts can decide whether they are fair and consistently applied.
There are parallels between the present discussion and the discussion about universal health coverage. WHO defines universal health coverage as “all people receiving quality health services that meet their needs without being exposed to financial hardship in paying for them.”33 Given resource constraints, this does not mean that all possible services or technologies—including medicines—should be covered; the expansion of health coverage must be aligned with reasonable social goals.34
WHO’s guidance through its model list is valuable because it represents the judgment that direct acting antivirals for HCV infection are safe and potentially cost effective. However, it does not settle—and does intend to settle—many important priority setting decisions facing countries with different HCV prevalences and health system capacities. Countries still face the difficult task of making resource allocation decisions that create winners and losers. In pluralist societies we are likely to encounter reasonable disagreements about the principles that should govern such decisions. A fair, deliberative process is necessary to establish the legitimacy and fairness of such decisions.35 36 Key elements of fair process will involve transparency about the grounds for decisions; appeals to rationales that all can accept as relevant to meeting health needs fairly; procedures for challenging and revising decisions; and mechanisms for enforcing the previous three conditions. Together, these elements assure “accountability for reasonableness.” We propose that countries adapt this framework of accountability in designing a fair process to decide whether the newly listed “essential” hepatitis drugs should be made available, and for whom.
The addition of direct acting antivirals for HCV infection to WHO’s model list does not mean every country should make them universally available
Treating everyone who could benefit is likely to be unaffordable for most health systems given the high disease prevalence
Countries need to take account of the full opportunity cost of using the drugs
They should adapt the accountability for reasonableness framework in designing a fair process to decide whether the drugs should be made available and for whom
Contributors and sources: JU works on human rights, health policy, health system reform, and priority setting. TP has experience in health policy and global health. ND has written widely on health inequalities, priority setting, ageing and equity, and health system reform. All the authors contributed to the conception of the work. JU contributed to the collection and interpretation of related information, and prepared the draft of the manuscript; TP and ND contributed to critical revisions of the manuscript. JU is the guarantor of the article. All authors verified the final version.
Competing interests: We have read and understood BMJ policy on declaration of interests and have no interests to declare.
Provenance and peer review: Not commissioned; externally peer reviewed.